Botox as a Treatment for Interstitial Cystitis in Women

Botox (Botulinum Toxin A) as a Treatment for Interstitial Cystitis in Women: A Randomized Placebo Controlled Trial

Patients with interstitial cystitis have been well documented to have pelvic floor muscle tenderness as well as pain on bladder distension. Some investigators have even suggested that pelvic floor muscle pain is primarily the cause of bladder problems.

Botulinum toxin A causes muscle relaxation by inhibiting the acetylcholine release at the neuromuscular junction. It has been shown that this mechanism relieves pain in a number of muscle spasm-related syndromes.

Because, at present, there is little effective therapy available for patients with interstitial cystitis, the researchers want to determine if botulinum toxin A will relieve bladder and pelvic pain in these patients.

Study Overview

• Status: Completed
• Conditions: Interstitial Cystitis; Painful Bladder Syndrome
• Intervention / Treatment: Drug: Botox; Other: normal saline

Detailed Description

Screening Visit:

After being screened by her medical provider, the patient will be given the opportunity to ask questions about the study. She will then be asked to read and sign the consent and then be randomized.

Then, for women of childbearing age, a pregnancy test will be done.

Next, we will ask the patient to fill out baseline study forms and she will be given a Voiding Diary. She will also be asked to provide a urine sample which will be processed for chemistry and culture.

Injection Visit:

This visit will be scheduled one week after the Screening Visit. First, a standard history and physical will be done. Then the clinician will proceed with the injection. The subject will receive an injection of not more than 5 ml of 1% lidocaine without epinephrine at the site of the botulinum toxin A injection.

Next, 25 units of Botox will be injected, via the transvaginal route, on either side of the bladder neck. The remaining 50 units will be injected (in 2 - 25 unit doses) into other pelvic sites that the patient has identified as tender during the patient examination.

1 Month Post Injection Mailing: The patient will be mailed a packet containing follow-up questionnaires and asked to mail them back upon completion.

6 Week Urine Collection Visit: Two weeks after receiving her study injection, we will ask the patient to go to the Urology Clinic and provide a urine sample.

2 Month Post Injection Mailing: Same as 1 Month Post Injection Visit.

3 Month Post Visit: The subject will be asked to fill out follow-up questionnaires and will be asked to turn in her last set of Voiding Diaries.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women ages 18 and older
• Diagnosis of interstitial cystitis
• Subject has severity/stage of disease: at least 12 voids/day with the presence of pelvic pain
• Ability to follow study instructions and likely to complete all required visits.
• Negative urine pregnancy test on the day of treatment prior to the administration of study medication (for females of childbearing potential; if applicable)

Exclusion Criteria:

• Use of any medications that might interfere with neuromuscular function
• Any medical condition that may put the subject at increased risk with exposure to Botox including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other disorder that might interfere with neuromuscular function
• Females who are pregnant, breast-feeding, or planning a pregnancy during the study or who think that they may be pregnant at the start of the study, or females of childbearing potential who are unable or unwilling to use a reliable form of contraception during the study
• Known allergy or sensitivity to any of the components in the study medication
• Concurrent participation in another investigational drug or device study, or participation in the 30 days immediately prior to study enrollment.
• Stress incontinence
• Urinary tract infection at time of enrollment
• Overtly psychotic or suicidal
• Pain from another source in the genital tract such as kidney stones or neoplasm
• Having had radiation therapy
• History of genitourinary tuberculosis
• Neurological abnormalities such as stroke, brain tumors, spinal cord injury and Parkinson's or Alzheimer's disease
• Currently taking antibiotics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botox injection; Subjects were injected with Botulinum toxin A in a mix of 50 U diluted in 2 cubic centimeters of normal saline. With the subjects in the dorsal lithotomy position, one injection of 25 international units was given into the bladder neck at the 3 o'clock position and another of 25 international units was given into the 9 o'clock position	Drug: Botox; Botox 25 international units per injection injected in two places in the bladder neck, with option to inject two other tender points with 25 units each; Other Names: Botulinum Toxin A
Placebo Comparator: Normal saline; Subjects were injected in the bladder neck with 1 cubic centimeter normal saline into the 3 o'clock and 6 o' clock positions in the perineum, while in the dorsal lithotomy position	Other: normal saline; Normal saline injected into the bladder neck via the perineum, 1 cc each given at positions 3 o'clock and 9 o'clock

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic Prostatitis Symptom Index (CPSI-F)	CPSI-F was adapted from the CPSI, in order to document the location of pain, with working pertinent to female anatomy. The CPSI-F was scored on a range of 0-83 (0-61 in the pain domain, 0-10 in the urination domain, 0-6 in the impact of symptoms domain, and 0-6 in the quality of life domain), with higher scores denoting worse symptoms.	3 months

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Paul G. Allen Family Foundation

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 19, 2005

Study Record Updates

• Last Update Posted (Estimate): October 12, 2012
• Last Update Submitted That Met QC Criteria: September 12, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Cystitis; Cystitis, Interstitial; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A
• Other Study ID Numbers: 25398-D